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The Role of the Endocannabinoid system in eating

Cakes, Porto, Portugal

This morning we also had a visit from Dr Vincenzo di Marzo of the Biomolecular Chemistry Institute, Pozzuoli, Italy. He has been working with a group of researchers studying the endocannabinoid system and how it is involved with food intake and eating disorders.  I wrote a brief summary of what I learned…

Cannabinoid comes from the word cannabis and some of the molecules used in the body’s endocannabinoid system are similar to the active ingredient of cannabis, Δ9- tetrahydrocannabinol. Mostly, the endocannabinoid system is separate to the influences of cannabis as a herb/drug/medicine.

There are two receptors for this system, CB1 which are found mostly in the brain but also in the digestive system and CB2 which are found outside the brain. Endocannabinoid molecules are produced and released when needed by cells, they act locally and are metabolised immediately after action.

The endocannabinoid system plays a vital role in the triggering of hunger and satiety. Endocannabinoid levels go up in the hypothalamus when food has not been consumed for a while and fall again while eating. In longer term starvation, this system becomes depressed, reducing the cravings for food which could be detrimental when food is unavailable. If mice have the CB1 receptor deactivated in the hypothalamus, they consistently eat half the amount of normal mice.

Endocannabinoids in the mesolimbic system give pleasure from certain types of food, especially high carbohydrate/fat ones through the production of dopamine. This system is also involved with the searching for high quality foods. CB1 inhibition in this area removes the pleasure from eating and if re-uptake of the endocannabinoids is suppressed, more food is eaten. This is one area where cannabis does influence the system, stimulating appetite (for which it has long been used in traditional medicinal systems).

Endocannabinoids are used for signalling in the gastrointestinal system, including the triggering of gastric emptying and intestinal secretions and motility. Again, this is another area cannabis ingestion affects, and it has traditionally been used as a treatment for diarrhoea.

Due to evolving with fluctuating food supplies, we have a system of storing energy as fat. Modern diets with constant supplies of high-energy foods often overwhelm this system leading, in extremes, to obesity. Key to the problem of obesity is the endocannabinoid system’s role in adipose or fat deposits. Mice with the CB1 receptor knocked out store less fat than normal mice with the same diet, they also have a higher metabolism and energy expenditure. On the other hand, CB1 receptor stimulation increases white adipocyte lipid creation and glucose uptake. PPARδ is a protein involved in the regulation of this adipose system and Dr di Marzo told us that physical exercise has been found to stimulate the production of PPARδ thereby reducing the creation and deposit of adipose tissue. Regular exercise is therefore extremely important in the treatment of obesity.

Due to the efficiency of CB1 receptor inhibition in reducing weight, pharmaceutical companies have worked to produce agents for this inhibition. These are now available but they have been found to significantly worsen depression/anxiety, so mostly they are prescribed only to those who have no history of depression, which greatly reduces the potential user-base due to obesity often being a cause of depression. Another drawback is that these drugs allow diet and exercise factors to remain unchanged, so their effectiveness requires continuous usage in the future to prevent regaining weight.

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